On May 19, 2023 KaliVir Immunotherapeutics, Inc., a biotech company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapy programs, reported the presentation of new data on its lead pre-clinical candidate VET3-TGI at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 26th Annual Meeting (Press release, KaliVir Immunotherapeutics, MAY 19, 2023, View Source;cell-therapy-asgct-annual-meeting-301829030.html [SID1234631886]).
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VET3-TGI is based on KaliVir’s unique Vaccinia Enhanced Template (VET) platform, capable of generating potent novel oncolytic vaccinia viruses with modifications to maximize viral replication and enhance intravenous delivery and spread. Modifications grant VET3-TGI the expression of CXCR3, IL-12 and a TGF-β inhibitor, allowing for efficient trafficking to the tumor, activation of anti-tumor immune responses and the overcoming of local immunosuppressive activity.
The functionality and therapeutic activity of VET3-TGI were tested in multiple models, and the mechanism of action and toxicity profile were assessed. VET3-TGI was compared to control virus in three pre-clinical in vivo tumor models, and demonstrated potent therapeutic activity, including 100% complete responses, even at several logs below equivalent clinical doses and in the presence of pre-existing anti-viral immunity. Profound changes in the tumor microenvironment (TME) were observed in VET3-TGI treated mice, including polarization to a type-1 immune response and recruitment of cytotoxic T cells. Analysis of gene expression profiles revealed that VET3-TGI treatment was associated with a dramatic increase in type-1 inflammatory chemokines, and a concomitant decrease in the expression of TGFβ1-associated genes that are involved with immuno-suppression. Compared to control virus-treated mice, VET3-TGI showed improved delivery to tumors following systemic administration, as well as reduced systemic toxicity.
"This new in vivo data is very encouraging and is a further validation of VET3-TGI as our lead pre-clinical candidate," said Stephen Thorne, PhD, CSO and co-founder of KaliVir. "These results build upon our already robust in vitro data as we expand into the next phase to develop a human version of the virus for efficacy and toxicology testing."
Presentation details
Date:
Friday, May 19th 5:15 PM – 5:30 PM PT
Title:
Novel Oncolytic therapy VET3-TGI restricts TGFβ1 and augments Type-1 immune response in TME, leading to superior therapeutic efficacy in multiple preclinical tumor models.
Presented by:
Ravikumar Muthuswamy, Ph.D. Director of Immunology, KaliVir Immunotherapeutics
Location:
Los Angeles Convention Center, West Hall, Room 501 ABC